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Researchers Discover First Gene Linking Calorie Restriction to Longevity

In studies going back to the 1930'S, mice and many other species subsisting on a severely calorie-restricted diet have consistently outlived their well-fed peers by as much as 40 percent. But just how a diet verging on the brink of starvation extends lifespan has remained elusive.

Now, Andrew Dillin and his team have cracked open the black box of how persistent hunger promotes long life and identified a critical gene, called pha-4, that specifically links calorie restriction (CR) to longevity in studies performed in the roundworm Caenorhabditis elegans.

"After 72 years of not knowing how calorie restriction works, we finally have genetic evidence to unravel the underlying molecular program required for increased longevity in response to calorie restriction," says Dillin, an associate professor in the Molecular and Cell Biology Laboratory, who led the study published online in Nature.

Having identified a key link between calorie restriction and aging also opens the door to development of drugs that mimic the effects of calorie restriction and might allow people to reap health benefits without adhering to an austere regimen that only ascetics can endure.

The potential payoff for cutting to 60 percent of normal while maintaining a healthy diet rich in vitamins, minerals, and other nutrients, is huge. Currently it is the only strategy, apart from direct genetic manipulation, that consistently prolongs life and reduces the risk of cancer, diabetes, and cardiovascular disease, while staving off age-related neurodegeneration in laboratory animals from mice to dogs. Although some people are already imposing this strict regimen upon themselves, it is too early to tell whether calorie restriction will have the same effect in humans.